Molecular Biology

, Volume 48, Issue 1, pp 1–10

Molecular basis of Parkinsons’s disease linked to LRRK2 mutations

Reveiws

DOI: 10.1134/S0026893314010117

Cite this article as:
Pchelina, S.N., Emelyanov, A.K. & Usenko, T.S. Mol Biol (2014) 48: 1. doi:10.1134/S0026893314010117

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder whose symptoms are consistent with death of dopaminergic neurons in the substantia nigra of the brain. The pathogenesis of PD involves several factors, such as α-synuclein aggregation, oxidative stress, mitochondrial dysfunction, and activation of apoptosis, but the exact molecular mechanism of neurodegeneration remains obscure. PD is usually sporadic, while rare monogenic forms have been identified and described in the past 15 years. Familial Parkinson’s disease is most commonly associated with mutations of the leucine repeat-rich kinase 2 gene (LRRK2). The mechanism of the disease due to LRRK2 mutations is unknown. The signaling cascades regulated by LRRK2 are difficult to study because the physiological substrates of the enzyme are unidentified. The G2019S substitution has been found to be the most common LRRK2 mutation, facilitating a search for patients with LRRK2-associated PD in various populations. The review considers the effects of LRRK2 mutations on protein and, in particular, α-synuclein aggregation, cytoskeletal dynamics, the inflammatory response, and the induction of apoptosis as revealed in both in vitro experiments and studies in PD patients. Investigation of rare hereditary PD forms with known etiology provides for a better understanding of the mechanism of neurodegeneration in more common sporadic PD forms.

Keywords

Parkinson’s disease hereditary forms LRRK2 α-synuclein aggregation apoptosis 

Copyright information

© Pleiades Publishing, Inc. 2014

Authors and Affiliations

  • S. N. Pchelina
    • 1
    • 2
    • 3
  • A. K. Emelyanov
    • 1
    • 2
    • 3
  • T. S. Usenko
    • 1
    • 2
  1. 1.Konstantinov Institute of Nuclear PhysicsNational Research Center Kurchatov InstituteGatchinaRussia
  2. 2.Ministry of Health of the Russian FederationPavlov St. Petersburg State Medical UniversitySt. PetersburgRussia
  3. 3.St. Petersburg Academic University—Nanotechnology Research and Education CenterRussian Academy of SciencesSt. PetersburgRussia

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